Tear is a thin liquid layer having a thickness of about 7 μm and covering the outermost layer of a ocular surface. The tear has a three-layer structure comprising, from the surface, a lipid layer, an aqueous layer and a mucin layer, and these layers influence one another to form the structure of the tear film. Further, each of the layers of the tear contains various components such as proteins, e.g., lactoferrin, lysozyme, IgA, IgG and albumin, wax, cholesterol, glucide, and mucin. Illustrative examples of the functions of the tear containing these components include keeping the ocular surface wet, preventing the eyes from infection with pathogens coming from the outside, supplying a number of physiologically active substances, and supplying oxygen to the cornea that is an avascular organ.
As described above, tear has a variety of functions. However, for example, when the amount of secretion of the tear is decreased due to the occurrence of dysfunction in secretion of the tear or when the amount of evaporation of the tear is increased due to the occurrence of dysfunction in the quality of the tear, the functions of the tear may not be exercised normally. When such tear dysfunctions occur, desiccation of the eyes is found as a subjective symptom. In recent years, along with an increased level of desiccation in a room due to wide use of air conditioners and increase of VDT operations on personal computers and the like, the number of patients who complain about discomforts caused by tear dysfunctions, such as desiccation of the eyes, foreign-body sensation, feeling of discomfort on the eyes and eye strain has been increasing. Further, a symptom in which an injury has occurred on the keratoconjunctive epithelium along with such tear dysfunctions is defined as dry eye. However, in the broad sense, even a case where dysfunctions in the secretion and quality of tear are seen and no injury is seen on the keratoconjunctive epithelium is also considered as suspected dry eye. Thus, it is conceived that by using an ophthalmic composition having an effect of treating tear dysfunctions, e.g., increasing the amount of secretion of tear or reducing the amount of evaporation of tear by improving the quality of the tear, discomforts caused by tear dysfunctions, such as desiccation of the eyes, foreign-body sensation, feeling of discomfort on the eyes and eye strain can be improved, and development of diseases caused by tear dysfunctions, such as dry eye and suspected dry eye which are dysfunctions related to desiccation of the eyes can be inhibited. Illustrative examples of the dry eye and suspected dry eye include diseases such as hypolacrimation, alacrima, xerophthalmia, Sjogren's syndrome, Stevens-Johnson syndrome, ocular pemphigus, marginal blepharitis, dysfunctions of lidaperture and sensory nerves, dry eye associated with allergic conjunctivitis, viral conjunctivitis and cataract operation, BUT-shortened dry eye characterized in that only a tear film breakup time (hereinafter abbreviated as “BUT”) which is one of the test method for diagnosis of tear is shortened, and symptoms caused by VDT operations which have been increasing in recent years.
At present, as a method of alleviating discomforts such as desiccation of the eyes and a method of alleviating or treating dry eye and suspected dry eye, a method comprising applying artificial tear from the outside to cover a deficiency of tear and a method comprising closing punctum are known, for example. Further, to treat injuries on the keratoconjunctive epithelium which have occurred due to dysfunctions in the secretion and quality of tear, a method using eye-drops containing sodium hyaluronate is also known, for example. However, the effects of all the above methods are temporary. Further, these methods are intended to treat injuries on the keratoconjunctive which are caused by tear dysfunctions and cannot inhibit the occurrence of dry eye and suspected dry eye and are merely symptomatic treatments. For these reasons, these methods are unsatisfactory. Therefore, not such symptomatic treatments as described above, but, for example, an ophthalmic composition having an effect of preventing desiccation of eyes and an ophthalmic composition for treating tear dysfunctions have been needed so as to improve discomforts caused by tear dysfunctions, such as desiccation of the eyes, foreign-body sensation, feeling of discomfort on the eyes and eye strain and to inhibit the occurrence of dry eye and suspected dry eye.
Heretofore, to prevent desiccation of the surface of the keratoconjunctive, an eye drop which contains glucomannan as an active ingredient (for example, refer to Patent Publication 1) and an eye solution which contains trimethylglycine (for example, refer to Patent Publication 2) have been disclosed. Further, it is also disclosed that a composition containing a β2 adrenaline receptor agonist as an active ingredient can be used as an agent for treating or preventing diseases related to dry eye or the keratoconjunctive sicca (for example, refer to Patent Publication 3).
Further, as preparations for treating dry eye, in the test method for diagnosis of tear such as BUT, a dry eye treating agent which contains a macrolide compound having an excellent improving effect as an active ingredient (for example, refer to Patent Publication 4) and a composition for treating tear secretion dysfunctions including dry eye which contains a fatty acid derivative as an active ingredient (for example, refer to Patent Publication 5) are disclosed.
Meanwhile, with respect to 3-hydroxybutyric acid which is used as an active ingredient in the present invention, the present applicant has proposed a therapeutic agent for ectocornea injury (for example, refer to Patent Publication 6) and a cornea turbidity inhibitor (for example, refer to Patent Publication 7) as ophthalmic therapeutic preparations containing 3-hydroxybutyric acid as an active ingredient. However, with respect to an ophthalmic composition containing 3-hydroxybutyric acid, no reports have been made on use thereof for preventing desiccation of eyes and for treating tear dysfunction.    Patent Publication 1 JP-A 6-345653 (the term “JP-A” as used herein means an “unexamined published Japanese patent application”)    Patent Publication 2 JP-A 2000-281563    Patent Publication 3 WO01/041806    Patent Publication 4 JP-A 2002-543132    Patent Publication 5 JP-A 2003-504397    Patent Publication 6 JP-A 10-265378    Patent Publication 7 JP-A 2001-89366